Gene Editing Technology Holds Huge Potential

A new gene editing technology known as CRISPR-Cas9 is taking the scientific community by storm. It is based on a system that bacteria use to defend themselves and their descendants against viruses that can make them sick (yes, bacteria can get sick). Over the last few years, researchers have used this system to precisely alter protein coding genes (genes that provide instructions for making proteins) in human cells, mice, rats, zebrafish, fruit flies and plants. In some cases, disease causing mutations in a protein have been corrected with CRISPR-Cas9, offering some hope for therapeutic intervention.

Now, for the first time, researchers from the Aab Cardiovascular Research Institute (CVRI) at the University of Rochester have used CRISPR-Cas9 to change a regulatory element – a non-protein coding snippet of DNA that controls a gene’s expression – in the laboratory mouse.

“To our surprise, we found that by making a very subtle change in DNA using the CRISPR-Cas9 technology we were able to virtually wipe out the expression of a gene,” said lead study author Joseph Miano, Ph.D., associate professor and associate director of the CVRI. “With this revolutionary technology scientists can literally edit any nucleotide in the 3 billion-plus nucleotides that make up the blueprint of mammalian life forms, including humans.”

According to Miano, the study of these snippets of DNA is extremely relevant because most disease-causing mutations occur in the 98.5 percent of the human genome that does not code for proteins. He says that what was once considered junk DNA is in fact replete with non-coding genes and millions of snippets of DNA that dictate if and when genes are turned on or off and for how long. He says we can now easily model variations in key regulatory snippets that occur in humans predisposed to certain diseases. His study was published earlier this year in the journal Arteriosclerosis, Thrombosis and Vascular Biology.

“Dr. Miano’s study is especially relevant for our understanding of gene regulation,” said Brian L. Black, Ph.D., professor and associate director of the Cardiovascular Research Institute at the University of California, San Francisco. “This represents the first study of its kind, where a single transcription factor binding site in noncoding DNA has been mutated in the context of the otherwise completely intact genome. This work has broad implications for discovery-based basic science and for the mechanisms of disease.”

While several scientists across the country have published studies using the CRISPR-Cas9 system, Miano’s team is the first to report on its use in upstate New York.

“CRISPR-Cas9 is a huge game changer and it will be a staple in all labs interested in modeling or finding ways to combat human diseases,” noted Miano. He credits the University’s Gene Targeting and Transgenic Facility, led by Lin Gan, Ph.D., for making the research possible.

In addition to Miano, Yu Han, Orazio Slivano and Christine Christie from CVRI contributed to the research, as well as Albert Cheng from Jackson Laboratories in Bar Harbor, Maine.

The CRISPR-Cas9 method is being hailed as one of the most innovative developments in biology and talk of a Nobel Prize is abuzz.

“In my nearly 30 years of working in science I have never experienced such a dramatic shift in how I go about my day-to-day work,” concluded Miano. “I would not be surprised if a Nobel Prize on CRISPR-Cas9 is awarded in the next couple of years."

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